Frequently, it is desirable to mask or protect the reactivity of heteroatoms during the course of multi-step organic syntheses. A textbook that summarizes the utility of a wide variety of heteroatom protecting groups has been published by Peter G. M. Wuts and Theodora W. Greene (Greene's Protective Groups in Organic Synthesis, Wiley, 2006). Oxycarbonyl protecting groups such as Cbz, Boc, Fmoc, and the like are known to in the art. For example, N-Boc or N-Fmoc protection strategies are used in automated solid-phase peptide synthesizers that are currently available. Similarly, triarylmethyl protecting groups such as DMT, MMT, Tr, and the like are known to those skilled in the art. For example, the O-DMT protection strategy is used in automated oligonucleotide synthesizers that are currently available.
Colorimetric analysis of synthetic intermediates during the course of multi-step syntheses on solid supports such as peptide synthesis, oligonucleotide synthesis, polysaccharide synthesis, and combinatorial chemistry is a valuable means for assessing the result of key synthetic steps. For example, in automated, solid-supported peptide synthesis, monitoring the characteristic absorbance of 1-((9H-fluoren-9-yl)methyl)piperidine during the cleavage of an Fmoc protecting group from the amino terminus of the growing peptide provides valuable information as to the progress of the synthesis. Similarly in automated, solid-supported oligonucleotide synthesis monitoring the absorbance of light at a wavelength of about 498 nM, which is indicative of the DMT-cation that is produced during the cleavage of a DMT protecting group from the 5′-hydroxyl terminus of the growing oligonucleotide, provides valuable information as to the progress of the synthesis. Similarly in automated, solid-supported polysaccharide synthesis and combinatorial chemistry the calorimetric monitoring of the presence of primary amino groups with a ninhydrin test provides valuable information as to the progress of the synthesis.
The 2-(4-nitrophenyl)sulfonylethoxycarbonyl protecting group, which provides an enhanced calorimetric signal upon basic cleavage as compared to the Fmoc protecting group, has been described by Ramage et al. (Journal of Peptide Science, 5(4), 199-200, 1999). The preparation and characterization of a homologous series of solid phase synthesis resins for anchoring amines via a Boc-like linker has been described by Hernandez et al. (Journal of Organic Chemistry, 62(10), 3153-7, 1997). The 4-(4-nitrophthalimido)butyrate protecting group for alcohols, which provides a calorimetric signal upon cleavage with hydrazine acetate has been described by Ko et al. (Organic Letters, 10(23), 5381-4, 2008). The protection of alcohols by treatment with the symmetrical anhydride of 5-(3-(hydroxybis(4-methoxyphenyl)methyl)phenoxy)-4-oxopentanoic acid and the subsequent deprotection with a hydrazine-pyridinium acetate buffer at nearly neutral pH to provide a calorimetric signal have been described by Leikauf et al. (Tetrahedron, 51(19), 5557-62, 1995).